Preliminary studies suggest that the in vivo metastasis and growth patterns of lymphomas may be determined and/or predicted by their ability to interact with endothelial cells, particularly the specialized post-capillary, high endothelial venules (HEV) in lymphoid organs that mediate the exit of normal migrating lymphocytes from the blood. In the mouse, initial studies with AKR lymphomas indicate that lymphomas that are unable to recognize and bind to HEV tend to grow primarily locally, whereas HEV-binding lymphomas exhibit early symmetric involvement of all secondary lymphoid organs regardless of the route of injection. These murine studies will be continued in order to define rigorously the relationship between HEV-recognition ability and the patterns of spread of lymphomas in this animal model system. In addition, in the first year of this grant, we have made substantial progress towards extending these studies to humans by: (1)\adapting an in vitro frozen section assay to the measurement of human lymphocyte-HEV interaction and (2)\producing a monoclonal antibody, 9B5, that we believe defines human lymphocyte surface homing receptor(s) for HEV. Studies in the coming year will attempt to link the 9B5 antigen with its presumed function. Once we have confirmed this specificity, we will begin to apply this antibody, as well as the functional HEV binding assay, to the study of homing receptor expression by non-Hodgkin's lymphoid malignancies in order to correlate HEV receptor expression with histologic type and clinical behavior. These studies have the potential to identify an important functional and molecular correlate of the in vivo growth and spread of murine and human lymphomas and leukemias. They should provide us with ethical means of studying the migratory properties of normal and malignant lymphocytes in man. (L)